We recently found a non-plasma, abnormal protein, from patients with hereditary nephritis and hereditary nephritis with deafness (Alport's Syndrome). We hypothesize that this protein directly reflects the biochemical defect that is responsible for the ultrastructural abnormality of glomerular basement membrane in this disease. The objective of the proposed study is to learn the molecular basis of hereditary nephritis by biochemical and immunological comparison of the abnormal urinary protein with membrane proteins of normal kidney. Specific aims and methods include: purification of the urinary protein by chromatography and electrophoresis; development of an immunological assay of the protein for purposes of rapid urine screening; immunological localization of the protein in normal kidney and in renal biopsy sections from hereditary nephritis patients; isolation of cross-reacting protein from normal kidney; analysis of the urinary protein and the supposed homologous protein from kidney for differences in amino acid sequence or attached oligosaccharides; and structural comparison on purified urinary protein from different families for determination of possibly allelic mutations. This study has the potential to provide bases for biochemical diagnosis of hereditary nephritis in the absence of renal biopsy and family studies, and perhaps to provide the basic knowledge from which specific treatment for the disease could be developed.